Evaluación del riesgo cardiovascular en pacientes con disrupción del ritmo circadiano en prevención secundaria, en pacientes sometidos a una intervención dietéticas (dieta mediterránea o dieta baja en grasas)
- Autores: Juan Luis Romero Cabrera
- Directores de la Tesis: Antonio García Ríos (dir. tes.), José López Miranda (dir. tes.)
- Lectura: En la Universidad de Córdoba (ESP) ( España ) en 2023
- Idioma: español
- Tribunal Calificador de la Tesis: Manuel Castro Cabezas (presid.), Francisco Fuentes Jiménez (secret.), Mercedes Sotos Prieto (voc.)
- Materias:
- Enlaces
- Tesis en acceso abierto en: Helvia
- Resumen
1. Introducción o motivación de la tesis:
Cardiovascular disease continues to be a major cause of morbidity and mortality. Despite several efforts to control and management traditional risk factor by physicians, researchers and governments it is not enough to reduce the cardiovascular burden.
Chronodisruption has emerged as a novel risk factor linked for cardiovascular diseases. In this order, certain population have demonstrated to be prone to suffer chronodisruption such as shift workers or evening subjects. Thus, evening subjects have showed to have unhealthy lifestyle habits with later meal timing, activity and sleep timing, potential mechanisms associated with the high cardiometabolic risk linked to evening subjects.
Our hypothesis was demonstrated that those patients prone to suffer circadian rhythm disruption (i.e. evening chronotype) with unhealthy lifestyle habits, present higher cardiometabolic risk based in greater endothelial dysfunction and increased cardiometabolic and inflammatory markers.
Main objective: - To investigate whether patients in secondary prevention with a disruption of the circadian rhythm (unregulated sleep pattern, physical activity and an unusual meal schedule) have, at baseline, greater endothelial dysfunction as measured by flow-mediated vasodilation (FMD) of the brachial artery.
Secondary objectives: - To determine whether participants following a Mediterranean diet with 35% of daily calories from fat (22% monounsaturated fat) or a low-fat diet with 28% of daily calories from fat (12% monounsaturated fat) for three years will improve endothelial function in participants with disruption of circadian rhythm.
- To determine whether the disruption of the circadian rhythm is associated with increased inflammatory markers (C-reactive protein (CRP), Interleukins).
- To investigate whether whose participants with a disruption of the circadian rhythm show a higher oxidative stress.
2.Contenido de la investigación:
The CORDIOPREV study is a randomized single-blind, controlled dietary intervention trial in coronary heart diseases (CHD) patients. The models of diet intervention included in the CORDIOPREV study were: the Mediterranean diet, with a minimum 35% of calories as fat (22% monounsaturated fatty acids (MUFA)) and a maximum of 50% carbohydrates and the low-fat diet comprising of <30% total fat (12%-14% MUFA fat), and a minimum 55% carbohydrates. The chronotype was assessed using the Morningness-Eveningness questionnaire in 857 participants from the CORDIOPREV study. At the beginning of the CORDIOPREV study and after 1,5 years, the flow mediated vasodilation in the brachial artery was assessed. Lifestyle habits were obtained through questionnaire at baseline of the study and yearly. Meal and sleep timing of one-week duration were collected during first years of the study. Baseline and annual visits included blood samples, blood pressure and anthropometric measures. In a sub-set of participants (n=168) ambulatory circadian monitoring were recorded and non-parametric analyses were used to calculate circadian-related parameters.
There were no significant differences in endothelial dysfunction according to chronotype at baseline either after 1.5 years of a healthy dietary intervention. No differences were found between the two models of diet. However, evening subjects demonstrated high cardiovascular risk with higher cardiometabolic and inflammatory markers such as HDL-C (p 0.04), homocysteine (p<0.01), hs-CRP (p 0.01) and triglycerides (p<0.01) at baseline of the study and during the four first year of the follow-up despite a healthy dietary intervention compared to morning subjects. Also, evening subjects had a higher prevalence of MetS (OR 1.58 IC 95% [1.10-2.28], p 0.01). Differences in several lifestyle habits according to chronotype were found. Thus, evening subjects were less active (p 0.01) and more sedentary (p<0.01), evening subjects had later meal timing of three main meals (p<0.01) and later sleep timing (p 0.01) and longer sleep duration (p 0.02) than morning subjects. In the sub-set of participants that the ambulatory circadian monitoring was performed, evening subjects showed lower amplitude (p=0.04), greater fragmentation (p=0.04), less stable pattern day to day (p<0.01), and lower robustness (p<0.01) of the TAP rhythms and lower regular habits (p<0.01) compared to morning subjects. A correlation of the lifestyle factors and circadian-related parameters with cardiometabolic and inflammatory markers were demonstrated.
3.Conclusión:
Our findings showed that evening individuals with preexisting CHD had a higher cardiometabolic risk due to their propensity for chronodisruption. Evening subjects has worse lifestyles factors and circadian health compared to morning subjects that could influence as potential mechanism of the high cardiometabolic risk found. Our finding support to assess chronotype in high-risk population to target personalized and tailoring recommendations and reduce their cardiovascular burden.
4. Bibliografía:
1. Romero-Cabrera JL, Garaulet M, Jimenez-Torres J, Alcala-Diaz JF, Quintana Navarro GM, Martin-Piedra L, Torres-Peña JD, Rodriguez-Cantalejo F, Rangel-Zuñiga OA, Yubero-Serrano EM, Luque RM, Ordovas JM, Lopez-Miranda J, Pérez-Martínez P, García-Rios A. Chronodisruption and diet associated with increased cardiometabolic risk in coronary heart disease patients: the CORDIOPREV study. Transl Res. 2022 Apr;242:79-92. doi: 10.1016/j.trsl.2021.11.001. Epub 2021 Nov 6. PMID: 34752950.
2. Delgado-Lista J, Perez-Martinez P, Garcia-Rios A, Alcala-Diaz JF, Perez-Caballero AI, Gomez-Delgado F, Fuentes F, Quintana-Navarro G, Lopez-Segura F, Ortiz-Morales AM, Delgado-Casado N, Yubero-Serrano EM, Camargo A, Marin C, Rodriguez-Cantalejo F, Gomez-Luna P, Ordovas JM, Lopez-Miranda J, Perez-Jimenez F. CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (the CORDIOPREV study): Rationale, methods, and baseline characteristics: A clinical trial comparing the efficacy of a Mediterranean diet rich in olive oil versus a low-fat diet on cardiovascular disease in coronary patients. Am Heart J. 2016 Jul;177:42-50. doi: 10.1016/j.ahj.2016.04.011. Epub 2016 Apr 27. PMID: 27297848; PMCID: PMC4910622.
